Complete Donor T-Cell Chimerism Predicts Lower Relapse Incidence after Standard Double Umbilical Cord Blood Reduced Intensity Conditioning Regimen Allogeneic Transplantation in Adults

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2479-2479
Author(s):  
Pierre Peterlin ◽  
Jacques Delaunay ◽  
Thierry Guillaume ◽  
Thomas Gastinne ◽  
Beatrice Mahe ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Cord Blood ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Allogeneic Transplantation ◽  
Reduced Intensity Conditioning Regimen ◽  
Before And After ◽  
The Impact

Abstract Double umbilical cord blood (dUCB) allogeneic transplantation following low dose TBI, cyclophosphamide and Fludarabine (TCF regimen)-based reduced-intensity conditioning regimen (RIC) is increasingly used in adults lacking a suitable related or unrelated donor. Currently, there is little data regarding the impact on long-term outcome of CD3+ T cell chimerism (TCC) in this particular setting. Thirty-six adults with various hematological diseases and who receieved dUCB conditioned with TCF were included in this retrospective study. Peripheral blood CD3+ TCC was considered until day +100 post-tranplant in order to determine the impact of full versus mixed chimerism on long-term outcomes. Twenty-nine and 7 patients were documented with full and mixed CD3+ TCC, respectively, within the first 100 days post-transplant. With a median follow-up of 36 months, 3 year-OS, DFS, and relapse incidence were 61%, (95% CI 43-75); 50% (95% CI 32.5-66) and 28% (95% CI 16-44), respectively. In univariate analysis, a full CD3+ TCC was associated with a better 3-year DFS : 59% (95% CI 39-75.5) versus 14% (95% CI 7-46), (HR=0.24 [0.09-0.65], p=0.005) and a lower cumulative incidence of relapse : 24% (95% CI 21.5-57) versus 78% (95% CI 52-99), (HR=0.18 [0.05-0.5], p=0.004). In multivariate analysis, a full CD3+ TCC remained associated with a lower incidence or relapse (HR=0.17, 95% CI 0.028-0.99, p=0.049). CD3+ TCC has no impact on GVHD and NRM in this study. In conclusion, in our study, full CD3+ TCC was independently associated with a lower risk of relapse after dUCB TCF RIC allogeneic transplant in adults, highlighting the need to develop immunotherapy approaches allowing for early conversion to full chimerism after dUCB. Abstract 2479. Table 1 Patients, sustained cord blood and transplantation characteristics. Patients, sustained cord blood and transplantation characteristics Full TCC (n=29) Mixed TCC (n=7) p No.of patients % No.of patients % Patients characteristic Age at transplant, years, median (range) 57 (22-69) 47 (17-64) NS Sex female 14 48 3 43 NS Hematological malignancy : Lymphoid / myeloid 14 / 15 48 / 52 3 / 4 43 / 57 NS Statut at transplant : RC / RP 23 / 6 79 / 21 6 / 1 86 / 14 NS Time to transplant, days, median (range) 395 (137-5645) 216 (92-604) NS Cord blood characteristics Age of cord blood, months, median (range) 31 (9-165) 116 (23-140) NS Matching cordon with patient NS 4/6 10 35 3 43 5/6 19 65 3 43 6/6 0 0 1 14 Number of total nucleated cell 10^8/kg before and after thawing, respectively, median (range) 0,28 (0,16-0,455) ; 0,248 (0,157-0,406) 0,222 (0,135-0,492) ; 0,22 (0,11-0,392) NS Number of CD34+ cell 10^6/kg before and after thawing, respectively, median (range) 0,066 (0,022-0,215) ; 0,043 (0,02-0,2) 0,078 (0,031-0,427) ; 0,041 (0,019-0,259) NS Mismatch between cord blood and patient Sex 14 48 3 43 NS Serology CMV 13 45 3 43 NS ABO 16 55 2 28 NS Rhesus 22 76 6 86 NS Graft Neutrophil count recovery >0.5 G/L, days, median (range) 17 (6-32) 11 (7-20) NS Platellet recovery >20G/L, days, median (range) 41 (0-164) 31 (0-67) NS Acute GVHD (grade II-IV / grade III-IV) 19 (12 / 6) 65 (41 / 21) 4 (3 / 1) 57 (43 / 14) NS Chronic GVHD (Limited / Extensive) 11 (8 / 3) 38 (28 / 10) 3 (2 / 1) 43 (28 / 14) NS Chimerism Rate, %, median (range) 100 (96-100) 82 (14-94) <0,001 Table 2 Multivariate analysis for DFS, OS and CIR. Multivariate analysis Hazard Ratio 95% CI P values DFS Age (continuos variable) 0.97 0.93 to 1.01 0.174 Sex 0.37 0.10 to 1.26 0.111 TCC full versus mixed 0.28 0.074 to 1.04 0.058 Chronic GVHD : noversus yes 4.68 1.12 to 19.53 0.034 OS Age (continuous variable) 0.95 0.91 to 0.99 0.022 myeloid vs lymphoid 9.13 1.7 to 49.05 0.010 Acute GVHD : none vs grade 3-4 0.24 0.06 to 0.93 0.038 TCC full versus mixed 0.62 0.15 to 2.46 0.495 CIR Age (continuos variable) 0.95 0.91 to 1.00 0.057 Sex 0.88 0.15 to 5.26 0.892 TCC full versus mixed 0.17 0.028 to .99 0.049 Chronic GVHD : no versus yes 8.19 0.46 to 146.41 0.153 Disclosures No relevant conflicts of interest to declare.

The Use of Bone Marrow Graft for Hematopoietic Stem Cell Transplantation From Matched Unrelated Donors After Reduced Intensity Conditioning Regimen Improves Survival : Analysis of the Societe Française De Greffe De Moelle Et De Therapie Cellulaire.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 873-873
Author(s):  
Andrea Toma ◽  
Marie-Lorraine Balère-Appert ◽  
Jean-Michel Boiron ◽  
Pierre Bordigoni ◽  
Gerard Socie ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multivariate Analysis ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Reduced Intensity Conditioning ◽  
Hematopoietic Stem ◽  
Reduced Intensity Conditioning Regimen ◽  
Unrelated Donors ◽  
Grade Ii

Abstract Abstract 873 The use of peripheral blood stem cells (PBSC) for hematopoietic stem cell transplantation (HSCT) is associated with a higher risk of chronic graft versus host disease (GvHD) but its impact on survival is not clear since it may favor a greater graft versus leukemia (GvL) effect. However, in the context of HSCT from unrelated donors (UD), the balance between GvH and GvL may differ from the context of sibling donors and thus the use of PBSC may be deleterious. In this retrospective study, we analyzed 103 patients from the french registry who received a graft from an UD after a reduced intensity conditioning regimen (RIC) to evaluate the role of various parameters including the source of stem cells on the outcome. Seventy-one D/R pairs (69%) were 10/10 HLA match at the allelic level. Mismatches concerned 5, 6, 15, 2 and 7 D/R pairs for HLA-A, -B, -C, -DRB1 and -DQB1, respectively. The median age was 46 years (18-67). All patients had hematologic malignancies: AL (n=35), MM (n=18), CLL (n=5), NHL (n=11), HD (n=9), CML (n=12), MDS (n=9), and MPS (n=4). 39% of the patients were in an advanced phase of the disease at time of HSCT. The conditioning regimen was Fluda/TBI 2Gys for 26 patients, Bu/Fluda/ATG for 24 patients, Fluda/Melph for 16 patients and others for 37 patients. Overall, anti-thymocytes globulins (ATG) were part of the conditioning regimen for 77% of patients. The source of stem cells was PBSC for 65 patients and bone marrow (BM) for 38 patients. The median follow up of the cohort is 61,3 months (1,2-113,7). The results showed that 95% of patients engrafted. Five patients did not engraft (4 in the BM group and 1 in the PBSC group). Acute GvHD grade II to IV and grade III/IV occurred in 47% and 19% of patients, respectively. The risk of developing chronic GvHD was 49% at 2 years. Overall survival (OS) was 36% at five years. The median disease free survival (DFS) was 55 months among the 36 patients alive. We performed univariate and multivariate analysis of factors susceptible to impact on GvHD and survival. The multivariate analysis included the impact of HLA mismatch, disease status, diagnosis, source of stem cells, patient's and donor's ages. This multivariate analysis performed on the global population shows a trend towards an improved OS with the use of BM instead of PBSC. However, when focusing the multivariate analysis on the 71 patients transplanted with a 10/10 match donor, the most potent factor influencing the outcome is the use of BM which is associated with an improved OS (p=0.03) and DFS (p=0.02), less acute GvHD grade II-IV (p=0.05), or grade III/IV (p=0.05) and less chronic GvHD (p=0.05). These results suggest that the use of BM as the source of stem cells should be reconsidered in the context of matched UD after RIC transplantation. Disclosures: No relevant conflicts of interest to declare.

Unrelated Allogeneic Stem Cell Transplantation for Severe Acquired Aplastic Anemia: Has Outcome Improved?.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3105-3105 ◽  
Author(s):  
Sebastien Maury ◽  
M.-Lorraine Balere-Appert ◽  
Zina Chir ◽  
J.-Michel Boiron ◽  
Claire Galambrun ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Aplastic Anemia ◽  
Graft Failure ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Young Patients ◽  
Unrelated Donor ◽  
Hla Matching ◽  
The Impact

Abstract We aimed to determine whether outcome of HSCT from an unrelated donor has improved over time for patients with severe acquired aplastic anemia (SAA) and, if so, to determine whether improvement resulted from changes in patient selection, changes in transplantation technique, or both. We thus analyzed the outcome of 89 patients (median age 17 years, range 0–52) who received such transplantations between 1989 and 2004. We compared two cohorts of patients transplanted within two successive time-periods (1989–1998 and 1999–2004) associated with probabilities (± 95% confidence interval) of 5-year survival significantly different: 29% ± 7% and 50% ± 7%, respectively (P<.01, Figure 1). Significant differences between the two cohorts concerned transplant-related, but not patient- and disease-related variables: the use of ATG and of fludarabine within conditioning and HLA matching at the allelic level for the 10 HLA-A, -B, -C, -DRB1 and -DQB1 loci (P=.0004) were more frequent in the recent 1999–2004 period. In multivariate analysis, the only 2 factors influencing survival were HLA allelic matching (P<.01) and younger age of recipient (<17 years, P<.0001). Of note, the impact of HLA matching disappeared in multivariate analysis when it was considered at the antigenic level for HLA-A, -B and -DR antigens, which underlines the importance of considering HLA matching at the allelic rather than the generic level for these transplantations. Survival reached 78% ± 11% at 5-year for the younger patients fully HLA-matched (n=14), which can be compared with survivals obtained for HLA-identical sibling transplants in similar young patients. Cumulative incidences of graft failure, grade II–IV or grade III–IV acute GVHD, and chronic GVHD were: 14% ± 4 % at 2 years, 50% ± 5 % and 24% ± 4 % at 100 days, and 28% ± 5 % at 2 years after HSCT (limited: 17% ± 4 %, extensive: 11% ± 3 %), respectively. In a competing risk analysis, allelic HLA matching - particularly incorporating HLA-C but not -DQB1 matching - but also a high cell-dose injected (> 2,6.108/kg nucleated cells, the median value of the cohort) and the use of fludarabine and/or ATG in the conditioning regimen were found as protective against graft failure and acute GVHD, respectively. Our results suggest that survival after unrelated transplantation for SAA has improved over the past 15 years, due to a better HLA matching at the allelic level for both HLA class I and class II antigens, but also to other transplant-related factors. Figure 1 Figure 1.

Influence of CD34+ and CD3+ Graft Content on Gvhd Development after Haploidentical Allogeneic Transplantation with Post-Transplant Cyclophosphamide

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3131-3131
Author(s):  
Mariana Bastos-Oreiro ◽  
Pascual Balsalobre ◽  
Diana Champ ◽  
Juan Churruca ◽  
Maria Jesus Pascual ◽  
...  
Keyword(s):  
Acute Gvhd ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Patient Characteristics ◽  
Allogeneic Transplantation ◽  
Hematologic Malignancies ◽  
Post Transplant ◽  
Cell Dose ◽  
The Impact

Abstract Introduction: CD34+ and CD3+ cell dose in peripheral blood stem cell (PBSC) graft have been related with increased incidence of graft versus host disease (GVHD) in some transplant settings. Our aim in this study was to evaluate the impact of CD34+ and CD3+ cells graft composition on GVHD incidence in the setting of haploidentical transplant (haplo-HSCT) with post-transplant cyclophosphamide (PT-Cy), in a multicenter analysis. Materials (or patients) and methods: We retrospectively evaluated 175 patients with hematologic malignancies who were treated with a haplo-HSCT from 2011 to 2014 with PBSC in GETH centers. All patients received Busulfan-Fludarabine as conditioning regimen and GVHD prophylaxis was performed with PT-Cy (50 mg/kg on days +3 and +4) and a calcineurin inhibitor plus mycophenolate from day +5. We analyzed the impact of CD34+ and CD3+ cell doses (low vs. high with cut-off at the median value, and the 25-75 percentiles) on the development of acute and chronic graft versus receptor disease. Death before GVHD development was considered as a competitive event. The analysis was adjusted for conditioning intensity. STATA software was used for data analysis Results: We analyzed 175 patients. Patient characteristics are resumed in table 1. Median CD34+ and CD3+ cell dose was 5.31x10e6/kg (p 25-75: 4.31-6.1) and 2.07x10e8/kg (p25-75: 1.19-2.94), respectively. Cumulative incidences of grade II-IV acute GVHD and all grades chronic GVHD was 32.6% and 30% respectively. The median follow-up was 12.3 months (r:6-46). No difference in terms of GVHD (acute and chronic), was found between low and high CD34+ cell doses. However, if we focus on T cells, high doses of CD3+, for values above the median, have been has been associated with increased incidence of acute GVHD II-IV (day 150: 47% vs 26% p=0.01, figure 2), as well as cGVHD (30 month: 39% vs 16%, p= 0.01 figure 1). If we focus the analyses regarding the intensity of conditioning regimen, the influence of CD3+ doses remains for the group of reduced-intensity conditioning (RIC) (aGVHD, day 150: 54% vs 24%, p=0.003; cGVHD, 30 month: 47% vs 16%, p=0.006 figure 2), but lost for patients who receive myeloablative intensity (aGVHD, day 150: 33% vs 33% p=0-8; cGVHD, 30 month: 21% vs 16%, p=0.81) Conclusion: In our series, in the setting of haplo-HSCT with Pt-Cy, the highest dose of lymphocytes was associated with a higher incidence of aGHVD II-IV and cGV HD, especially for the RIC procedures. Disclosures No relevant conflicts of interest to declare.

Outcome and Immune Reconstitution Following T Cell Depleted Nonmyeloablative Allogeneic Transplantation Using Matched Donors.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2036-2036 ◽  
Author(s):  
David A. Rizzieri ◽  
Liang Piu Koh ◽  
Gwynn D. Long ◽  
Cristina Gasparetto ◽  
Jerald Z. Gong ◽  
...  
Keyword(s):  
T Cell ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Immunosuppressive Agents ◽  
Allogeneic Transplantation ◽  
Stable Phase ◽  
Immune Recovery ◽  
Post Transplant ◽  
Donor Cells

Abstract To minimize toxicity and monitor immune recovery without interference of long term use of immunosuppressive agents, we have investigated T-cell depleted, nonmyeloablative allogeneic therapy using matched family member donors. Methods: Seventy five patients who were not candidates for ablative therapy due to age or comorbid diseases received fludarabine 30mg/sq m and cyclophosphamide 500mg/sq m IV qd x 4 with alemtuzumab 20mg IV qd x 5 followed by stem cell infusion. No other post transplant immunomodulation was provided. Results: Patient diagnoses included lymphoma/myeloma (20), leukemias/MDS (30), myelofibrosis/aplasia (7) and metastatic solid tumours (18). The median age was 50 (range 18–17) with a median follow up of 18 months. The median CD34+ cell dose collected was 13.4 x 106/kg. Engraftment occurred in 100% of patients with a median of 97% donor cells responsible for patient hematopoiesis by 3 months. Forty six also had a DLI (range 106–108 CD3+ cells/kg). Overall, Grade III–IV acute GVHD occurred in only 5/75 (7%) and 18 (29%) had grade II–IV. Four patients developed chronic GVHD. The transplant regimen was well tolerated with 4% 100 day treatment related mortality. In those with hematologic malignancies, only 7% started in remission, though 45 (60%) attained a CR. The most common cause of death in this group was progressive disease (28%), followed by infections (5%), and GVHD (5%). A subgroup of 21 of these older, more infirm patients who had high risk AML in 1–2nd CR or PR or ≥2 chronic stable phase CML, partially responding lymphoma, or severe myelofibrosis have been followed for at least 1 year. At 1 year, 13/21 (62%) remain alive and in continuing remission. Phenotypic analysis of lymphocyte subsets (measured by flow) revealed recovery at 6 months. Figure Figure T cell VBeta family recovery (spectratype analysis using PCR) revealed robust recovery by 6 months as well (first figure pre and second is 6 months post transplant), despite T depletion. Figure Figure TRECs analysis reveals little, if any, recovery in these patients for at least 12–18 months. Conclusions: Nonablative allogeneic transplantation using alemtuzumab for T cell depletion results in reliable engraftment with little acute GVHD or TRM. Immune recovery assays reveal that despite T cell purging, T cell subset and VBeta families have significant recovery by 6 months and TRECS results show the recovery is primarily from peripheral expansion of transplanted donor cells, not education of new T cells. These data possibly reflect the advantage of low dose donor lymphocyte boosts without planned long term use of immunosuppressive agents. The future challenge will to be to develop strategies to further improve immune recovery in this setting.

Outcomes of 40 Adult Patients after Double Cord Blood Transplantation Using a Reduced Intensity Chemotherapy Conditioning Regimen.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 605-605
Author(s):  
Karen K. Ballen ◽  
Corey Cutler ◽  
Thomas R. Spitzer ◽  
Beow Yeap ◽  
Steve McAfee ◽  
...  
Keyword(s):  
Cord Blood ◽  
Total Dose ◽  
Aplastic Anemia ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Cord Blood Unit ◽  
Reduced Intensity ◽  
Related Mortality

Abstract Umbilical cord blood is an alternative stem cell source for patients without matched related or unrelated donors. However, single cord blood unit transplantation in adults is associated with high transplant related mortality, mostly due to infection. In this study, we used a reduced intensity conditioning regimen followed by infusion of two partially matched cord blood units. The conditioning regimen was fludarabine 30mg/m2/day Days -8,-7,-6,-5,-4,-3 (total dose 180mg/m2), melphalan 100mg/m2/day Day -2, and rabbit antithymocyte globulin (thymoglobulin) 1.5 mg/kg/day Days -7,-5,-3,-1 (total dose 6.0 mg/kg). Cord blood units were a 4/6 or better HLA A, B, DR match with each other and with the patient, and contained a minimum combined pre-freeze cell dose of 3.7 x 107NC/kg. GVHD prophylaxis was cyclosporine and mycophenolate mofetil, for the first 21 patients, and tacrolimus and sirolimus for the second cohort of 19 patients. Forty patients, 22 males (55%) and 18 females (45%) with a median age of 48 years (range 19–64 years) were treated. The diagnoses were AML (n=14), ALL (n=1), NHL (n=10), CLL (n=2), MDS (n=5), Hodgkins Disease (n=5), aplastic anemia (n=2), and chronic myelogeneous leukemia (n=1). Thirty-five patients have greater than 100 days of follow-up and are included in this analysis. The cell doses infused were a median of 4.0 x 10 7NC/kg (range 3.0–6.7 x 107) and 1.9 x 10 5 CD34+ cells/kg (range 0.5–10.0 x 105). Two patients (both with MDS complicating aplastic anemia) experienced primary graft failure, and received second cord blood transplants using a different conditioning regimen. Among the remaining patients, the median time to an absolute neutrophil count &gt;500 was 21 days (range 14–70 days). There were two late graft failures. The median time to a platelet count &gt;20,000 unsupported was 43 days (range 21–125 days). The incidence of acute GVHD Grades II–IV was 40% for the patients receiving cyclosporine/MMF and 29% for patients receiving tacrolimus and sirolimus. There were no deaths from acute GVHD in the cyclosporine/MMF group and one death from acute GVHD in the tacrolimus/sirolimus group. Seven patients (20%) developed chronic GVHD. The 100-day transplant related mortality was 14%. Two deaths were related to Epstein Barr virus related lymphoproliferative disorder, and the other deaths were due to a CNS bleed, staphylococcal sepsis, and respiratory failure due to aspergillus infection. Two patients have relapsed and one has progressive disease. With a median follow up of 14 months (range 3–31 months) the overall survival is 74% and the disease-free survival is 67%. Chimerism analysis showed predominance of one cord by Day +100. In 71% of patients, the first cord blood unit infused predominated. In conclusion, engraftment of adult patients appears to be acceptable using double cord blood products and reduced intensity, non TBI conditioning regimen; the risk of serious acute and chronic GVHD is low, survival is excellent in a selected group of patients and relapse rate is low, suggesting preservation of graft versus leukemia effect despite the low T cell dose.

Unrelated Cord Blood Transplantation: Comparison After Single Unit Cord Blood Intrabone Injection and Double Unit Cord Blood Transplantation In Patients with Hematological Malignant Disorders. A Eurocord-EBMT Analysis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 223-223 ◽  
Author(s):  
Vanderson Rocha ◽  
Myriam Labopin ◽  
Annalisa Ruggeri ◽  
Marina Podestà ◽  
Dolores Caballero ◽  
...  
Keyword(s):  
Cord Blood ◽  
Median Time ◽  
Acute Gvhd ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Adult Patients ◽  
Myeloablative Conditioning ◽  
Blood Transplantation ◽  
Gvhd Prophylaxis ◽  
The Impact

Abstract Abstract 223 The use of single cord blood unit for transplantation in adult patients is limited due to the high risk of graft failure and delayed neutrophil and platelet recoveries. The limited hematopoietic progenitors in UCB grafts and their homing after IV injection, have prompted investigators to study the design of delivering CB grafts directly into the bone marrow (BM) space (IBCBT) or to use double cord blood transplantation (dUCBT) to improve engraftment. To evaluate the impact of IBCBT, we made a retrospective based registry comparison with dUCBT performed in the same time period (2006-2010) and reported to Eurocord-EBMT. We included 87 and 149 patients who received either IBCBT or dUCBT, respectively, after a myeloablative conditioning regimen for malignant disorders. IBCBT was performed in 8 EBMT centers whereas dUCBT was performed in 56 EBMT centers. Majority of patients in both groups had acute leukemia. IBCBT patients were older (p<0.001), more frequently received an autologous graft (p<0.001) and had positive CMV serology (p<0.001), and importantly had more advanced disease at transplantation (p=0.04). Median number of infused (after thawing) nucleated cells injected intrabone was 2.5×107/kg and it was 3.9×107/kg in dUCBT (p<0.001). In 72% of both groups, CB grafts were HLA 4/6 (the highest HLA disparity was taken into consideration in dUCBT). Other differences were regarding GVHD prophylaxis that was based on CSA+MMF in 100% of IBCBT and in 62% of dUCBT cases; ATG was used in all IBCBT and 40% of dUCBT. Median follow-up time was 18 months in IBCBT and 17 months in dUCBT. At day 30, cumulative incidence (CI) of neutrophil recovery (ANC >500) was 83% after IBCBT and 63% after dUCBT, and at day 60, it was 90% in both groups; the median time to reach ANC>500 was 23 and 28 days after IBCBT and after dUCBT (p=0.001) respectively. At Day-180 CI of platelets recovery was 81% after IBCBT and 65% after dUCBT (p<0.001) with a median time of 36 days and 49 respectively (p=0.002). At day 100, CI of acute GVHD (II-IV) was 19% and 47% (p<0.001) and chronic GVHD 34% and 37% respectively (p=NS) respectively. Unadjusted 2 years-CI of NRM and RI were 31% and 23% after IBCBT and 35% and 28% after dUCBT, respectively (p=NS). Unadjusted 2 y-DFS estimation was 47% after IBCBT and 37% after dUCBT (p=NS). In multivariate analysis adjusting for statistical differences between 2 groups (such as status of the disease at transplant, age, CMV, previous transplants, GVHD prophylaxis), recipients of IBCBT had improved DFS (HR: 1.64, p=0.035), faster platelet recovery (HR:2.13, p<0.001) and decreased acute GVHD (HR:0.31; p<0.001) compared to dUCBT recipients. We did not find a cut-off value of number of nucleated cells after IBCBT or dUCBT that could be associated with outcomes after both approaches. In conclusion, both strategies have extended the use of CB transplants to adults in need of cord blood transplantation. Therefore, IBCBT is an option to transplant adult patients with single CB units after myeloablative conditioning regimen and may impact the total costs of cord blood transplantation. Based on these results, intra-bone technique may disclose new transplant potentialities also with other HSC sources. Disclosures: No relevant conflicts of interest to declare.

Effects Of Noninherited Maternal Antigen On The Occurrence Of Acute Graft-Versus Host Diseae After Unmanipulated Haploidentical Blood and Marrow Transplantation

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3301-3301
Author(s):  
Ying-Jun Chang ◽  
Dai-Hong Liu ◽  
Kaiyan Liu ◽  
Lan-Ping Xu ◽  
Yu Wang ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Cumulative Incidence ◽  
Marrow Transplantation ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Graft Versus Host ◽  
Blood And Marrow Transplantation ◽  
High Incidence ◽  
Mismatched Donor

Abstract Background Exposure to non-inherited maternal antigen (NIMA) in fetal and neonatal life has a lifelong immunological consequence. In haploidentical transplantation, the mismatched haplotype of the donor can originate from either the mother or the father. The aim of this prospective study is to investigate the effects of NIMA and non-inherited paternal antigen (NIPA) on transplant outcomes in patients who underwent unmanipulated haploidentical blood and marrow transplantation (HBMT). Methods Two hundred and eleven patients with hematological disease, including AML, ALL, CML, MDS, SAA, and others, who received haploidentical blood and marrow allgrafts were enrolled in this study. The stem cell source was G-CSF mobilized BM combined with PB. The conditioning regimen was modified BUCY plus ATG with 10mg/kg in total dosage. MTX, CSA, and MMF were used for prophylaxis of graft-versus-host disease. Results The median patient follow-up was 343 days (range, 7-573 days). The median time for neutrophil and platelet engraftment was 12 days (range 7-25 days) and 16 days (range 6-410 days), respectively. The cumulative incidence of grade 2-4 actue GVHD at day 100 after HBMT was 41.7%±3.8% The cumulative incidence of chronic GVHD at 1 year was 53.4%±4.1%. The 1-year probability of relapse, TRM, LFS, and OS at 1 year was 11.3%±2.3%, 8.3%±1.9%, 79.6%±3.0%, and 85.0%±2.8%, respectively. Among the 211 patients, multivariate analysis showed that high risk patients had a high relapse rate (HR: 3.699, 95%CI, 1.598-8.565, P=0.002) and low LFS (HR: 2.452, 95%CI, 1.322-4.546, P=0.004). Duration from diagnosis to transplantation (more than 6 months vs. less than or equal to 6 moths) was associated with a high incidence of TRM (HR: 3.175, 95%CI, 1.251-8.059, P=0.015). Young recipient age (HR: 0.969, 95%CI, 0.946-0.993, P=0.012) were associated with a low incidence of grade 2-4 actue GVHD. Multiple analysis also showed that patients who received allografts from NIMA mismatched donor and father donor had lower incidences of grade 2-4 actue GVHD compared to those of patients receiving allografts from mother (HR: 0.576, 95%CI, 0.334-0.996, P=0.048, and HR: 0.378, 95%CI, 0.126-1.137, 0.087, respectively). For subgroup patients who received allografts from sibling donors, multivariate analysis showed that sibling transplantations mismatched for NIMA had a significantly lower incidence of grade 2-4 acute GVHD than those with NIPA mismatched donors (HR: 0.257, 95%CI, 0.083-0.796, P=0.018). No effects of NIMA mismatch on relapse, TRM, LFS, and OS were found in the current study. Conclusions Our results suggest that HBMT from a NIMA mismatched donor can offer low indicence of grade 2-4 acute GVHD. In unmanipulated haploidentical settings, mother donor transplantation may be associated with high incidence of grade 2-4 acute GVHD. These data suggest a NIMA mismatched donor not a mother donor should be preffered as donor for unmanipulated haploidentical blood and marrow transplantation. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Bone marrow transplantation in 107 patients with severe aplastic anemia using cyclophosphamide and thoraco-abdominal irradiation for conditioning: long-term follow-up

Blood ◽  
1991 ◽  
Vol 78 (9) ◽  
pp. 2451-2455 ◽  
Author(s):  
E Gluckman ◽  
G Socie ◽  
A Devergie ◽  
H Bourdeau-Esperou ◽  
R Traineau ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Multivariate Analysis ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Long Term Follow Up ◽  
Abdominal Irradiation

Since 1980, 107 consecutive patients (pts) underwent bone marrow transplantation (BMT) for nonconstitutional severe aplastic anemia (SAA) at our institution. All received conditioning with Cytoxan (150 mg/kg) and thoraco-abdominal irradiation (6 Gy) from an HLA-identical sibling donor. Mean age was 19 years (5 to 46 years). Forty-nine pts had less than 0.2 x 10(9)/L PMN and 53 failed to respond to previous immunosuppressive therapy before BMT. Graft-versus-host disease (GVHD) prophylaxis consisted of methotrexate (22 pts), cyclosporine (52 pts), or both (33 pts). With a median follow-up of 45 months (12 to 120 months), overall actuarial survival was 68% (confidence interval 95%:9.7). Of 16 factors tested, five were shown to adversely influence survival by multivariate analysis: grade greater than or equal to 2 acute GVHD (relative risk [RR]: 5.5), prior immunosuppressive therapy (RR: 3.5), female as donor (RR: 2.4), nonidiopathic SAA (RR: 2), and more than 0.2 x 10(9)/L PMN AA (RR: 2). Because acute GVHD was the most potent factor for survival, we analysed risk factors for acute GVHD. By multivariate analysis, 2 of 14 factors tested were independent: male as recipient (RR: 3) and previous alloimmunization of the donor (RR: 4.3). On long-term follow-up, chronic GVHD was observed in 49 pts of 89 surviving more than 100 days (55%). Multivariate analysis showed that infection before transplant (RR: 1.3) and previous history of acute GVHD (RR: 1.8) were associated with an increased risk of chronic GVHD.

scholarly journals Bone marrow transplantation in 107 patients with severe aplastic anemia using cyclophosphamide and thoraco-abdominal irradiation for conditioning: long-term follow-up

Blood ◽  
1991 ◽  
Vol 78 (9) ◽  
pp. 2451-2455 ◽  
Author(s):  
E Gluckman ◽  
G Socie ◽  
A Devergie ◽  
H Bourdeau-Esperou ◽  
R Traineau ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Multivariate Analysis ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Long Term Follow Up ◽  
Abdominal Irradiation

Abstract Since 1980, 107 consecutive patients (pts) underwent bone marrow transplantation (BMT) for nonconstitutional severe aplastic anemia (SAA) at our institution. All received conditioning with Cytoxan (150 mg/kg) and thoraco-abdominal irradiation (6 Gy) from an HLA-identical sibling donor. Mean age was 19 years (5 to 46 years). Forty-nine pts had less than 0.2 x 10(9)/L PMN and 53 failed to respond to previous immunosuppressive therapy before BMT. Graft-versus-host disease (GVHD) prophylaxis consisted of methotrexate (22 pts), cyclosporine (52 pts), or both (33 pts). With a median follow-up of 45 months (12 to 120 months), overall actuarial survival was 68% (confidence interval 95%:9.7). Of 16 factors tested, five were shown to adversely influence survival by multivariate analysis: grade greater than or equal to 2 acute GVHD (relative risk [RR]: 5.5), prior immunosuppressive therapy (RR: 3.5), female as donor (RR: 2.4), nonidiopathic SAA (RR: 2), and more than 0.2 x 10(9)/L PMN AA (RR: 2). Because acute GVHD was the most potent factor for survival, we analysed risk factors for acute GVHD. By multivariate analysis, 2 of 14 factors tested were independent: male as recipient (RR: 3) and previous alloimmunization of the donor (RR: 4.3). On long-term follow-up, chronic GVHD was observed in 49 pts of 89 surviving more than 100 days (55%). Multivariate analysis showed that infection before transplant (RR: 1.3) and previous history of acute GVHD (RR: 1.8) were associated with an increased risk of chronic GVHD.

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